While the earliest accounts in medicine date back to ancient civilizations, more recent scientific discoveries have fueled the progression of delivery system technologies. In 1862, John Wyeth, a pharmacist and researcher, manufactured medicines in large quantities for doctors and wholesale distribution. His commitment to the mass production of medicines led to the development of the ‘compressed pill’ or tablet and the invention of the rotary tablet press in 1872. Pharmaceuticals dispensed in tablet form allowed convenience in taking medication but still often required multiple administrations. The continued development of the modern pharmaceutical industry, especially since the 1950s, has led to a plethora of controlled release or time release technologies. These technologies have been used with numerous pharmaceuticals and can be divided into three categories—delayed release, site directed systems, and sustained or time release (Chaudhari, 2004).
Delayed release systems dispense repetitive doses of one or more active ingredients often utilizing parenteral release routes. These release routes include transdermal drug delivery, intravenous injections, intramuscular injections, or subcutaneous implants. Transdermal drug delivery systems are generally non-invasive, are aesthetically acceptable, can provide local delivery over several days, and can be used on unconscious patients (Kaparissides et al., 2006).
Site directed technologies are utilized in numerous biological systems to deliver active ingredients directly to targeted locations. Historically, these systems have been diffusion controlled; however, modern research is investigating biodegradable polymer systems (Vogelson, 2001). Targeted delivery systems include polymeric microspheres, microcapsules, nanocapsules, macromolecular complexes, and polymeric beads.
Sustained release systems are formulated to dissolve slowly and release a substance over time. These systems are generally formulated with an active substance embedded into a matrix of time release agents. These sustained release mechanisms allow active ingredients to escape through diffusion or through osmotic release, i.e., physical swelling to form a gel in which active ingredients are released through the surface of the product.
With the success of advanced delivery technologies, scientists have expanded the industry beyond pharmaceuticals to include various applications involved with agriculture and bioremediation. BIOCAPSULES (Center of Bioremediation, Salt Lake City, Utah) offer site-specific encapsulated microorganisms for sustained, delayed, and/or targeted release in environmental and bioremediation applications (http://programs.weber.edu/bioremediation/biocapsu.htm). The focus of BIOCAPSULES is to provide stable, simultaneous time release of microorganisms and key nutrients to environmental applications using a biodegradable matrix. Reference is also made to a product called BIOGREEN (BiogreenLTD, Melbourne, Vic, Australia) for sustained release insecticides in crop control. U.S. Pat. No. 5,472,955 to Kellerby is directed to sustained release insecticides for horn fly control. Further, a product called MICROESSENTIALS EZ (Cargill AgHorizons, Cargill Limited, Winnipeg, Manitoba, Canada) is directed to sustained release fertilizers for crop nutrition.
While sustained or time release technologies have not yet been utilized in fermentation applications, research has shown that balanced nutrition is extremely important to fermentation rate, cell growth, and fermentation kinetics (Chaney et al., 2006). Winemakers often are required to add additives at various stages of the fermentation to prevent stuck fermentations, to reduce or prevent formation of hydrogen sulfide, acetic acid, ethyl carbamate, and other unwanted metabolites as well as to improve aroma and flavor profiles.
The role of microbial supplementation via complex additives and nutrients containing assimilable nitrogen, vitamins, minerals, and amino acids has been well documented (Agenbach, 1977; Butzke, 1998; Ingledew and Kunkee, 1985; Ough et al., 1989; and Sablayrolles, et al., 1996). Research has shown that multiple additions are indeed superior to single additions (Alfenore et al., 2002; Chaney et al., 2006; Julien et al., 2000; and Manginot et al., 1998). Research suggests that adding all nutrient supplements simultaneously can lead to a rushed fermentation rate, an imbalance in uptake and usage of nitrogen compounds, and less fruity character of wines.
Addition of nitrogen to deficient juices is extremely important for cell growth, metabolism, protein synthesis, and alcohol resistance; however, the timing of the addition is equally as important. For instance, one large addition of diammonium phosphate initially can delay or inhibit the uptake of amino acids. Therefore, multiple additions over time are preferred and will keep the fermentation process at its peak increasing the reliability of the fermentation. Chaney et al. 2006 reported Shiraz grapes that received two nitrogen additions completed fermentation with low volatile acidity at standard temperature (29° C.); whereas, duplicate tanks with the standard nitrogen addition regime produced increased volatile acidity and failed to complete fermentation. Additive supplementation should be completed during the first half of fermentation.
Most winemakers do not have the option of performing multiple additions due to the volume of wine produced and time constraints during harvest.